“Starry liver” - Von Meyenburg complex clinical case presentation and differential diagnosis discussion: A case report

Table 1 Differential diagnosis criteria of polycystic liver disease, Caroli’s disease, and biliary hamartoma

	Polycystic liver disease	Caroli’s disease	Biliary hamartoma (VMC)
Epidemiology	From 1 to 10 cases per 1000000; M:F = 1:6[13]	From 0.01 to 1 in 1000000[7, 14]; M:F = 1:1[14]	In up to 5.6% of autopsies, an estimated 6% of the general population[1]; M:F = 1:1
Symptoms associated with a disease	20% of patients have dyspnea, early satiety, abdominal distension, malnutrition, gastroesophageal reflux, hepatomegaly, portal hypertension, ascites, and variceal hemorrhage[15]	Rarely portal hypertension or hepatomegaly, fever, hepatolithiasis, and gallbladder stones[16]	Normally absent; In rare cases, fever, jaundice, abdominal pain, and variceal hemorrhage[11]
Blood examination findings	Elevated GGT, ALP, AST, and total bilirubin are reported in some serious cases[15]; Possible elevation of CA19-9[17]	Transaminase levels may be slightly elevated; Thrombocytopenia and leukopenia if portal hypertension and/or hypersplenism are present; Leukocytosis and erythrocyte sedimentation rate may indicate cholangitis[16]	Possible elevation of liver enzymes (ALT, AST, ALP) and bilirubin; Rarely increased CA19-9[18]
Ultrasound/contrast-enhanced ultrasound	Hyperechoic areas in the subcapsular portion of the liver[11]; More than 20 hepatic cysts[19]; Larger in size compared to VMC[11]; Rarely uniform cysts, varying from < 1 mm to ≥ 12 cm in diameter; Diffuse dilatation of intra- and extrahepatic bile ducts[11]	Intrahepatic cystic anechoic areas in which fibrovascular bundles (composed of portal vein and hepatic arteries, which can be demonstrated by Doppler ultrasonography), stones and linear bridging or septum may be present[16]; Saccular or fusiform cystic dilatations of the intrahepatic bile ducts up to 5 cm in diameter often containing calculi[11]	Hypo- or hyperechoic lesions with comet-tail echoes, dot-sign; Small well-circumscribed lesions scattered throughout the liver with hypoechoic, hyperechoic, or mixed echogenicity depending on solid, cystic, or mixed components, respectively[12,19]; Hamartomas are relatively uniform in size[11]
Contrast-enhanced MRI, magnetic resonance cholangiopancreatography	Biliary ducts are not opacified with contrast; Cysts are round and smooth and are deformed but do not communicate with bile ducts[16]; Possible calcification of the walls of hepatic cysts[11]	Multiple small cystic formation is opacified with contrast; Present communication between the sacculi and bile ducts and diverticulum-like sacculi of the intrahepatic biliary tree; Cystic spaces are irregular in shape and communicate with biliary tree; Intrahepatic bile duct ectasia; Central dot sign[11,16]	Hypointense on T1-weighted images and hyperintense on T2-weighted sequences; Signal intensity is similar to the spleen but less intense than that of liver cysts[20]; MRI with gadolinium shows no communication between hamartomas and biliary ducts; Typical formation “starry sky”; Central dot sign[11]
Histological/ cytological evaluation	Multiple diffuse cystic lesions resembling solitary cysts, lined by cuboidal to flat biliary epithelium surrounded by fibrous stroma, with straw-colored fluid; 40% have identifiable VMCs[21]	Dilated bile ducts lined by cuboidal or columnar epithelium with fibrotic duct wall[22]	Bile ducts lined by cuboidal or flattened epithelium; Small to medium size[12]: Class 1: Mostly solid lesions with narrowing of biliary ducts; Class 2: Mixed solid/cystic lesions; Class 3: Mostly cystic lesions with ectasia of biliary ductsCytology findings of VMCs and bile duct adenomas are similar[12]
Treatment approach	No approved treatment; Optional pharmacological treatments of somatostatin receptor antagonists, mTOR inhibitor, vasopressin-2-receptor antagonists, estrogen receptor antagonists;surgical therapy: percutaneous cyst aspiration and sclerotherapy, laparoscopic cyst fenestration, segmental hepatic resection, and liver transplantation[15]	No specific treatment; Cholangitis must be handled with antibiotics, while cholestasis can be treated with ursodeoxycholic acid[23]; Antibiotics may stabilize the acute cholangitis; Drainage procedures with ERCP or PTC are important and sphincterotomy can aid biliary drainage and stone removal or subsequent passage and may decrease bouts of cholangitis; Lobectomy and liver transplantation[16,23]	VMC is considered a benign lesion that does not need any specific treatment unless complicated; In that case, a symptomatic treatment is prescribed (ursodeoxycholic acid or antibiotics)[12]
Complications, progression to cancer risk	Hemorrhage, infection, rupture, portal hypertension, jaundice, and end-stage liver disease[11,24]; Malignization is extremely rare[11]	Portal hypertension, cholangitis, sepsis, choledocholithiasis, hepatic abscess, cholangiocarcinoma and portal hypertension; Cholangiocarcinoma due to chronic inflammation of the biliary tree has been reported in 7%-14% of patients[11, 16,23]	Rarely persistent upper right quadrant pain; Rare calcifications, portal hypertension infectious cholangitis[2,3,5]; Lesions do not tend to grow[4]; Less than 3% probability of developing cholangiocarcinoma[1]

ALP: Alkaline phosphatase; ALT: Alanine transaminase; AST: Aspartate aminotransferase; CA19-9: Carbohydrate antigen 19-9; ERCP: Endoscopic retrograde cholangiopancreatography; F: Female; GGT: Gamma-glutamyl transferase; M: Male; MRI: Magnetic resonance imaging; mTOR: Mammalian target of rapamycin; PTC: Percutaneous transhepatic cholangiography; VMC: Von Meyenburg complex.